UC Irvine Researchers Restore Visual Function in Aging Eyes with Fatty Acid Supplement

Cientistas of Universidade of Califórnia in Irvine tested an approach that could pave the way for treating vision loss associated with aging. Eles injected a specific polyunsaturated fatty acid into the retina of aged mice. The results showed improvement in visual function. The research focuses on the direct product of the enzyme encoded by the ELOVL2 gene. Esse gene acts as a marker of aging and its activity decreases over time.

The team observed that aging reduces levels of very long-chain fatty acids in the retina. Essa shedding affects the health of photoreceptors and increases the risk of conditions such as age-related macular degeneration. The work, published in the journal Science Translational Medicine, represents an advance in relation to previous studies by the same group.

Gene ELOVL2 has a central role in retinal lipid metabolism

The ELOVL2 gene encodes an enzyme responsible for the production of precursors of essential fatty acids, including DHA and the so-called VLC-PUFAs. With advancing age, the expression of this gene drops. Older Camundongos show lower contrast sensitivity and slower dark adaptation. Modelos genes that block the enzyme’s activity confirmed the impact.

The researchers compared retinas from young and old animals. Lipidomic analysis revealed a significant reduction in long-chain fatty acids. Essa change accompanies worsening in the electrical responses of the retina measured by electroretinogram. The study also identified an accumulation of deposits associated with inflammatory processes.

• Análise showed a drop in VLC-PUFAs levels in the aged retina
• Modelos with ELOVL2 mutation reproduced symptoms of visual decline
• Injeção of compound 24:5n-3 increased the incorporation of specific phospholipids
• Scotopic and photopic Respostas improved after treatment
• Efeito lasted up to four weeks with a single dose in trials

Injeção of 24:5n-3 recovers visual responses without depending on the gene

The team bypassed the limitation of the ELOVL2 gene by directly delivering its immediate product. 18-month-old Camundongos received intravitreal injection of 24:5n-3 at a dose of 0.36 nmol. Cinco days later, electroretinogram recordings indicated a robust increase in wave amplitudes. Visually evoked Potenciais in the superior colliculus also rose.

The effect was specific. Suplementação with DHA or other related fatty acids did not produce the same result. Molecular analysis showed a reduction in the activation of oxidative stress and inflammation pathways. APOE-positive Depósitos and C3d in the sub-RPE region decreased. The researchers highlighted that the treatment rejuvenated lipidomic and transcriptomic profiles of the retina.

Short Parágrafos alternated with denser sequences to keep pace with findings. A long paragraph detailed the mechanisms. The next short reinforced the specificity of the compound.

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Variantes ELOVL2 genes associated with faster progression of macular degeneration

Dados from human cohorts indicated that certain variants in the ELOVL2 gene correlate with earlier onset of age-related macular degeneration. Essa genetic connection reinforces the gene’s role in the ocular aging process. The authors suggest that, in the future, tests could help identify individuals at higher risk.

The study did not test the treatment in humans. The results come from animal models and serve as proof of concept. Especialistas consider it necessary to move to experiments in larger animals before any clinical application. The intravitreal route of administration also requires optimization for long-term safety and efficacy.

Possíveis implications go beyond vision and affect the immune system

Colaborações parallels explore how lipid metabolism influenced by ELOVL2 affects aging immune cells. Lack of enzyme activity can accelerate age-related changes in the immune system. Suplementação systemic lipid appears as a hypothesis to mitigate these effects and potentially act in conditions such as hematological cancers.

The work integrates contributions from researchers at UC Irvine, Academia Polonesa from Ciências and Universidade from Saúde and Medicina from Potsdam, at Alemanha. Dorota Skowronska-Krawczyk, associate professor in the departments of Fisiologia and Biofísica and Oftalmologia and Ciências Visuais, leads the effort. Ela also integrates Centro Robert M. Brunson to Pesquisa Translacional from Visão.

Research reinforces the importance of very long-chain polyunsaturated fatty acids for retinal maintenance. Ela opens a line of investigation into therapies that act directly on lipids without depending on declining gene expression.

Próximos steps include replay tests and more complex models

The authors observed that repeated injections showed less gradual return of effect. Estratégias for sustained delivery or alternative formulations need development. Estudos in larger species will help assess viability for humans. The team continues to map connections between ELOVL2, lipid metabolism and other tissues affected by aging.